scholarly journals Targeted Expression of GLI1 in the Mammary Gland Disrupts Pregnancy-induced Maturation and Causes Lactation Failure

2007 ◽  
Vol 282 (49) ◽  
pp. 36090-36101 ◽  
Author(s):  
Marie Fiaschi ◽  
Björn Rozell ◽  
Åsa Bergström ◽  
Rune Toftgård ◽  
Marika I. Kleman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Hedgehog Signaling Pathway ◽  
Milk Protein Gene ◽  
Milk Protein Gene Expression ◽  
And Function

The Hedgehog signaling pathway regulates the development and function of numerous tissues and when mis-regulated causes tumorigenesis. To assess the role of a deregulated Hedgehog signaling pathway in the mammary gland we targeted the expression of the Hedgehog effector protein, GLI1, to mammary epithelial cells using a bigenic inducible system. A constitutively active Hedgehog signaling pathway resulted with 100% penetrance in an undifferentiated mammary lobuloalveolar network during pregnancy. GLI1-expressing transgenic females were unable to lactate and milk protein gene expression was essentially absent. The inability to lactate was permanent and independent of continued GLI1 transgene expression. An increased expression of the GLI1 response gene Snail coupled to reduced expression of E-cadherin and STAT5 in the transgenic mammary gland provides a likely molecular explanation, underlying the observed phenotypic changes. In addition, remodeling of the mammary gland after parturition was impaired and expression of GLI1 was associated with accumulation of cellular debris in the mammary ducts during involution, indicating a defect in the clearance of dead cells. Areas with highly proliferative epithelial cells were observed in mammary glands with induced expression of GLI1. Within such areas an increased frequency of cells expressing nuclear Cyclin D1 was observed. Taken together the data support the notion that correct regulation of Hedgehog signaling within the epithelial cell compartment is critical for pregnancy-induced mammary gland development and remodeling.

scholarly journals  Gene expression of six major milk proteins in primary bovine mammary epithelial cells isolated from milk during the first twenty weeks of lactation

2012 ◽  
Vol 57 (No. 10) ◽  
pp. 469-480 ◽  
Author(s):  
T. Sigl ◽  
H.H.D. Meyer ◽  
S. Wiedemann
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Milk Protein ◽  
Protein Gene ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Milk Protein Gene ◽  
Bovine Mammary Epithelial Cells ◽  
Milk Protein Genes ◽  
Milk Protein Gene Expression

&nbsp;The objective of the present study was to refine a previously developed method to isolate primary bovine mammary epithelial cells (pBMEC) from fresh milk. Using this method, it was tested whether the number of pBMEC and the relation of recovered pBMEC to total somatic cell count vary within the individual lactation stages. Furthermore, the expression levels of the milk protein genes during the first twenty weeks of lactation were determined by quantitative PCR method. A total number of 152 morning milk samples were obtained from twenty-four Holstein-Friesian cows during the first 20 weeks of lactation (day 8, 15, 26, 43, 57, 113, and 141 postpartum). Numbers of extracted pBMEC were consistent at all time-points (1.1 &plusmn; 0.06 to 1.4 &plusmn; 0.03 &times;10<sup>3</sup>/ml) and an average value of RNA integrity number (RIN) was 6.3 &plusmn; 0.3. Percentage of pBMEC in relation to total milk cells (2.0 &plusmn; 0.2 to 6.7 &plusmn; 1.0%) correlated with milk yield. Expression patterns of the casein genes alpha (&alpha;)<sub>S1</sub>, (&alpha;)<sub>S2</sub>, beta (&beta;), and kappa (&kappa;) (CSN1S1, CSN1S2, CSN2, CSN3, respectively) and the whey protein genes &alpha;-lactalbumin (LALBA) and progestagen-associated endometrial protein (PAEP; known as &beta;-lactoglobulin) were shown to be comparable, i.e. transcripts of all six milk protein genes were found to peak during the first two weeks of lactation and to decline continuously towards mid lactation. However, mRNA levels were different among genes with CSN3 showing the highest and LALBA the lowest abundance. We hypothesized that milk protein gene expression has a pivotal effect on milk protein composition with no influence on milk protein concentration. This paper is the first to describe milk protein gene expression during lactation in pBMEC collected in milk. Future studies will be needed to understand molecular mechanisms in pBMEC including regulation of expression and translation throughout lactation. &nbsp;

scholarly journals Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47876 ◽  
Author(s):  
Sonia M. Rosenfield ◽  
Emma T. Bowden ◽  
Shani Cohen-Missner ◽  
Krissa A. Gibby ◽  
Virginie Ory ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
And Function

scholarly journals The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vaibhav P. Pai ◽  
Laura L. Hernandez ◽  
Malinda A. Stull ◽  
Nelson D. Horseman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Serotonin Receptor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Mammary Epithelial ◽  
Lactation Performance ◽  
Epithelial Structure ◽  
And Function ◽  
First Time

Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer.

Gene expression in the mammary gland of the tammar wallaby during the lactation cycle reveals conserved mechanisms regulating mammalian lactation

2016 ◽  
Vol 28 (9) ◽  
pp. 1241 ◽  
Author(s):  
C. J. Vander Jagt ◽  
J. C. Whitley ◽  
B. G. Cocks ◽  
M. E. Goddard
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Milk Protein ◽  
Mammary Epithelial Cells ◽  
Tammar Wallaby ◽  
Mammary Epithelial ◽  
Molecular Networks ◽  
Milk Protein Gene ◽  
Milk Protein Gene Expression ◽  
Lactation Cycle

The tammar wallaby (Macropus eugenii), an Australian marsupial, has evolved a different lactation strategy compared with eutherian mammals, making it a valuable comparative model for lactation studies. The tammar mammary gland was investigated for changes in gene expression during key stages of the lactation cycle using microarrays. Differentially regulated genes were identified, annotated and subsequent gene ontologies, pathways and molecular networks analysed. Major milk-protein gene expression changes during lactation were in accord with changes in milk-protein secretion. However, other gene expression changes included changes in genes affecting mRNA stability, hormone and cytokine signalling and genes for transport and metabolism of amino acids and lipids. Some genes with large changes in expression have poorly known roles in lactation. For instance, SIM2 was upregulated at lactation initiation and may inhibit proliferation and involution of mammary epithelial cells, while FUT8 was upregulated in Phase 3 of lactation and may support the large increase in milk volume that occurs at this point in the lactation cycle. This pattern of regulation has not previously been reported and suggests that these genes may play a crucial regulatory role in marsupial milk production and are likely to play a related role in other mammals.

scholarly journals Correction: Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
Author(s):  
Sonia M. Rosenfield ◽  
Emma T. Bowden ◽  
Shani Cohen-Missner ◽  
Krissa A. Gibby ◽  
Virginie Ory ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
And Function

scholarly journals Mammary mechanobiology: mechanically-activated ion channels in lactation and involution

2019 ◽  
Author(s):  
Teneale A. Stewart ◽  
Katherine Hughes ◽  
Alexander J. Stevenson ◽  
Natascia Marino ◽  
Adler L. Ju ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Food Source ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mechanical Forces ◽  
Offspring Survival ◽  
Evolutionary Advantage ◽  
And Function ◽  
Mechanical Sensing

AbstractA mother’s ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by secretory mammary epithelial cells is adaptive, its release is exquisitely timed and its own glandular stagnation with the permanent cessation of suckling triggers the programmed cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals control epithelial expansion, function and remodeling. Despite this duality of input, however, the nature and function of mechanical forces in the mammary gland remain unknown. Here, we characterize the mammary force landscape and the capacity of luminal and basal epithelial cells to experience and exert force. We explore the molecular instruments for force-sensing in the mammary gland and the physiological requirement for PIEZO1 in lactation and involution. Our study supports the existence of a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.

scholarly journals Laminin alpha 5 is Necessary for Mammary Epithelial Growth and Function by Maintaining Luminal Epithelial Cell Identity

2019 ◽  
Author(s):  
Johanna I Englund ◽  
Hanne Cojoc ◽  
Leander Blaas ◽  
Alexandra Ritchie ◽  
Nalle Pentinmikko ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Normal Mammary Gland ◽  
Hormone Receptor Positive ◽  
And Function ◽  
Gland Development ◽  
Luminal Epithelial Cells ◽  
Basal Epithelial Cells

ABSTRACTEpithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we demonstrate that expression of distinct laminin α-isoforms by luminal and basal mammary epithelial cells enforces lineage identity that is necessary for normal mammary gland growth and function. Laminin α5 (LMα5) is mainly expressed by the luminal epithelial cells, and it is necessary for pubertal mammary gland growth, pregnancy induced gland remodeling, and for alveolar function. Adhesion to LMα5 containing laminin promotes luminal traits in both luminal and basal epithelial cells, and reduces progenitor activity of basal epithelial cells. Mechanistically, we show that Lama5 loss interferes with differentiation of hormone receptor positive luminal cells, which results in reduced Wnt4 expression and defective crosstalk between luminal and basal epithelial cells during gland remodeling. Our results reveal a novel BM-mediated mechanism, which regulates mammary gland remodeling and function via specification of luminal epithelial cells.

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